Ferroptosis Modulation, Cancer Therapeutics, and High-Purity Reagents for Selective GPX4 Development.
TarMart Solution Ecosystem & Related Targets
Comprehensive reagent toolkit for GPX4 drug discovery. Select your modality below:
| Component / Network | Product Description | Product Link |
|---|---|---|
| Antigen | GPX4 WT & Mutant Recombinant Protein (Sec-containing or Sec73Cys/Ser). High purity (>95%), Endotoxin <1 EU/ug. Sequence Verified. Ideal for SPR, structural assays, and MS adduct validation. | View GPX4 Products |
| Mutant Panel | GPX4 Catalytic Mutants (Sec73Cys, Sec73Ala, U46C). For mechanism studies, selectivity profiling, and overcoming selenocysteine instability. | View GPX4 Products |
| Isoform Panel | GPX1, GPX3, GPX6 orthologs (human, mouse, rat). For cross-family selectivity screening (GPX1-8 panel available). | View GPX1 Products |
| Gene Delivery | GPX4 Promise-ORF / Lentivirus (full-length ORF, shRNA). For stable overexpression or knockdown cell lines; native folding preserved. | View GPX4 Products |
| Benchmark Ab | Anti-GPX4 Reference Antibody (recombinant positive control). For western blot, IHC, and target engagement assays. | View GPX4 Products |
| Validator | GPX4 siRNA Set (3 independent sequences). For knockdown verification, synthetic lethality screening, and specificity confirmation. | View GPX4 Products |
| Related Target A | SLC7A11 (xCT). Cystine transporter upstream of GPX4; synergistic ferroptosis axis. | View SLC7A11 Products |
| Related Target B | FSP1 (AIFM2). Parallel ferroptosis suppression pathway; resistance bypass and combination therapy target. | View FSP1 Products |
| Related Target C | ACSL4. Lipid metabolism enzyme regulating ferroptosis sensitivity; biomarker for patient stratification. | View ACSL4 Products |
Critical Assay Challenges and TarMart Advantages
| Critical Assay Challenge | The TarMart Advantage (Technical Spec) |
|---|---|
| Subfamily counter-screening (GPX1/2/3/6/8 selectivity) | GPX homolog panel proteins strictly verified by mass spec; >95% purity for human, mouse, and rat orthologs. |
| Selenocysteine incorporation complexity & instability | Sec-containing GPX4 with verified UGA codon translation; Cys-mutant alternatives (Sec73Cys, U46C) for non-selenide assays and HTS/crystallography. |
| Covalent inhibitor off-target thiol reactivity | Active-site mutant proteins (Sec→Cys, Sec→Ser) available as negative controls for mechanistic deconvolution. |
| Lack of robust cellular controls for rescue assays | Lentivirus particles for stable GPX4 overexpression and knockdown lines; HEK293 packaging; validated siRNA for orthogonal readouts. |
| False positives in cell-based ferroptosis assays | Validated GPX4 siRNA sets included for rigorous genetic specificity checks before chemical inhibitor validation; benchmark antibodies for orthogonal readouts. |
| Activity quantification in biochemical assays | Coupled enzyme assay compatible (NADPH oxidation); validated Sec-dependent catalytic activity; lipid hydroperoxide substrate available. |
Live GPX4 R&D Tracker
Market data changes daily. Access the latest global pipeline status directly:
Global Clinical Landscape & Future Outlook
The race for GPX4-targeted therapeutics is intensifying around ferroptosis modulation in oncology. Unlike traditional apoptosis-targeting drugs, GPX4 inhibition exploits a unique vulnerability in lipid peroxidation-dependent tumor cell death, particularly in therapy-resistant "persister" cells and mesenchymal-state tumors. Major players (Bayer, Novartis, Eli Lilly, emerging biotechs) are shifting focus from first-generation covalent inhibitors (RSL3, ML210, ML162) with limited PK to highly selective non-covalent small molecules, allosteric binders, and PROTAC degraders. Concurrently, combination regimens (e.g., GPX4 inhibitors paired with immune checkpoint blockades or FSP1/ACSL4 modulators) are being pursued to bypass acquired resistance. For neurodegenerative applications (ALS, Parkinson's), brain-penetrant GPX4 activators or siRNA approaches are in early discovery. The next wave of R&D will address the narrow therapeutic window via tumor-selective delivery, short half-life design, or tissue-specific E3 ligase ligands for PROTACs.
Competitive Modality & Indication Snapshot
| Modality | Representative Players | Key Indications | Critical Assay Need (Why TarMart?) |
|---|---|---|---|
| Small Molecule (Covalent) | Bayer, Academic Labs (Stockwell, Conrad) | Therapy-resistant solid tumors, lymphoma, KRAS-mutant cancers | Adduct validation & selectivity: need high-purity WT vs Sec73Cys mutant proteins; GPX family panel for off-target screening. |
| Small Molecule (Non-Covalent) | Novartis, Eli Lilly, Emerging Biotechs | Clear cell renal cell carcinoma (ccRCC), solid tumors | Family selectivity panel (GPX1/3 proteins) and thermostability assays; need >100-fold selectivity to avoid renal toxicity. |
| PROTAC / Degrader | Arvinas, C4 Therapeutics, Undisclosed Biotechs | Refractory cancers, sarcoma, triple-negative breast cancer | Cell-based degradation assays: lentivirus for stable GPX4-HiBiT cell lines; knockdown validation tools (siRNA, antibodies). |
| siRNA / ASO / Gene Therapy | Alnylam, Silence Therapeutics | Neurodegeneration (ALS, Parkinson's), ischemia-reperfusion | Knockdown efficiency validation in CNS models; need validated siRNA controls and lentivirus-based stable cell lines for target engagement. |
Molecular Differentiation & Assay Strategy
Key Differentiation Elements
- Family Selectivity Barrier: GPX4 (monomer) must be distinguished from GPX1/3 (tetramers) to avoid systemic redox imbalance. High-throughput cross-screening with GPX1/3 recombinant proteins and NADPH-coupled kinetic assays is essential.
- Covalent vs Reversible Mechanism: Covalent inhibitors (e.g., ML210) require MS verification of Sec73 adduction and GSH competition assays; reversible inhibitors need thermal shift assays.
- Subcellular Localization: Three GPX4 isoforms (cytosolic, mitochondrial, nuclear) have distinct roles. Lentivirus-based isoform-specific overexpression lines enable localized activity profiling.
- Lipid Substrate Specificity: GPX4 reduces phospholipid hydroperoxides (PE-OOH), not H₂O₂. Assays require liposome-encapsulated hydroperoxide substrates.
TarMart Solution Alignment
| Differentiation Need | TarMart Product | Technical Spec Advantage |
|---|---|---|
| Sec incorporation verification | WT GPX4 + Sec73Cys mutant pair | Sequence-verified UGA codon; E. coli Sec insertion system; activity dependent on Sec. |
| Family selectivity screening | GPX1/3/6 recombinant protein panel | >40% homology to human GPX4; >95% purity for SPR/ITC. |
| Cellular validation | GPX4 ORF/shRNA Lentivirus | Stable KO/OE lines (HT-1080, PANC1); RSL3 sensitivity validation. |
| Mechanism & resistance preparedness | GPX4 mutant library (Sec73Ala, Arg152Ala, etc.) | Covers known resistance sites; enable screening of next-gen inhibitors overcoming Cys-substitution mutants. |
关联靶点推荐 (Cross-Selling Strategy)
Based on ferroptosis and lipid metabolism networks, we recommend cross-selling:
- SLC7A11 (xCT) – View SLC7A11 Products: Cystine transporter providing GSH precursors; synergy with GPX4 inhibition. Products: SLC7A11-ECD Fc fusion protein (antibody screening), SLC7A11 Lentivirus.
- FSP1 (AIFM2) – View FSP1 Products: Parallel CoQ10-dependent protection pathway; dual GPX4+FSP1 targeting is leading-edge. Products: FSP1 recombinant protein, iFSP1 reference compound.
- ACSL4 – View ACSL4 Products: PUFA esterification enzyme; high ACSL4 expression predicts GPX4 inhibitor sensitivity. Products: ACSL4 recombinant protein (enzyme assay), anti-ACSL4 antibody (IHC companion diagnostics).
Recommendation: Offer a "Complete Ferroptosis Solution" bundle: GPX4 protein + GPX1/GPX3 selectivity controls + SLC7A11/ACSL4 pathway proteins.